Activatable theranostic prodrug scaffold with tunable drug release rate for sequential photodynamic and chemotherapy  

作　　者：Si-Yu Wang Ying-Hao Pan Yu-Chen Qu Xiao-Xiao Chen Na Shao Li-Ya Niu Qing-Zheng Yang 

机构地区：[1]Key Laboratory of Radiopharmaceuticals,College of Chemistry,Beijing Normal University,Beijing,China [2]Department of Organic Chemistry,University of Geneva,Geneva,Switzerland

出　　处：《Smart Molecules》2024年第1期110-117,共8页智能分子（英文）

基　　金：support from the National Natural Science Foundation of China(22177014,22231001 and 21971023);the Fundamental Research Funds for the Central Universities and Key Laboratory of Photochemical Conversion and Optoelectronic Materials,TIPC,CAS.

摘　　要：Glutathione(GSH)-activated prodrugs are promising for overcoming the limitations of conventional anti-tumor drugs.However,current GSH-responsive disulfide groups exhibit unregulated reactivity,making it impossible to precisely control the drug release rate.We herein report a series of GSH-responsive prodrugs with a“three-in-one”molecular design by integrating a fluorescence report unit,stimuliresponsive unit and chemodrug into one scaffold with tunable aromatic nucleophilic substitution(SNAr)reactivity.The drug release rate of these prodrugs is tailored by modification of substituent groups with different electron-withdrawing or-donating abilities on the BODIPY core.Furthermore,the prodrugs self-assemble in water to form nanoparticles that serve as photosensitizers to produce reactive oxygen species upon irradiation for photodynamic therapy(PDT).The PDT process also increases the concentration of GSH in cells,further promoting the release of drugs for chemotherapy.This strategy provides a powerful platform for sequential photodynamic and chemotherapy with tunable drug release rates and synergistic therapeutic effects.

关 键 词：combinational therapy fluorescent probes photodynamic therapy PRODRUGS theranostic agents 

分 类 号：R73[医药卫生—肿瘤]